July 20, 2020

Ketosis

#120 – AMA with Dom D’Agostino, Ph.D., Part II of II: Ketosis for cancer and chronic disease, hyperbaric oxygen therapy, and the effect of ketosis on female health

"The function of the mitochondria and mitochondrial health are the ultimate mitigator of neurodegenerative diseases...just by reducing the potential for reactive oxygen species related damage." — Dom D’Agostino

Read Time 30 minutes

In part 2 of this special AMA episode, ketosis expert Dom D’Agostino once again joins Bob Kaplan, Peter’s Head of Research, to discuss the impact of ketosis on various chronic diseases as well as the latest research on the metabolic management of cancer. Dom also discusses the numerous applications of hyperbaric oxygen therapy, provides insights into the application of ketosis on female health and performance, and much more. If you’re not a subscriber and listening on a podcast player, you’ll only be able to hear a preview of the AMA.  If you’re a subscriber, you can now listen to this full episode on your private RSS feed or on the website show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

  • Update on Dom’s Press-pulse therapeutic strategy for the metabolic management of cancer [2:05];
  • Potential role for vitamin C in cancer treatment [12:45];
  • Glutamine targeting in cancer therapy—evidence that the mitochondria in cancer are damaged? [17:45];
  • Can a ketogenic diet lessen the toxicity of cancer therapies? [24:45];
  • 3BP—a promising agent in cancer therapy [26:45];
  • The relationship between cancer and ketogenic diets [29:30];
  • Hyperbaric oxygen therapy (HBOT)—primer, protocols, and therapeutic uses [33:30];
  • Is there a potential role for HBOT in treating COVID-19 patients? [44:15];
  • Non-cancer applications of HBOT [47:30];
  • The inverse relationship between glucose and ketones [50:30];
  • Is a ketogenic diet appropriate for type 1 diabetics? [54:00];
  • How ketosis may reduce the risk for Alzheimer’s disease and Parkinson’s disease [1:00:30];
  • Ketosis for females—considerations, fertility, performance, and the latest research [1:11:00];
  • Low-carb diets during pregnancy and postpartum [1:17:00];
  • A high-protein diet to counteract common hormonal issues associated with the ketogenic diet [1:21:15];
  • Nutritional tips for remaining metabolically flexible [1:22:45];
  • What is one belief Dom has changed his mind about? [1:26:45];
  • In utero experiments, and other interesting questions Dom wants to explore [1:29:45];
  • The anti-catabolic effect of ketones, cancer cachexia, and nutritional interventions for cancer patients [1:38:30];
  • What is the one interesting experiment Dom would do if money and time were no barrier? [1:46:25]; and
  • More.

§

Update on Dom’s Press-pulse therapeutic strategy for the metabolic management of cancer [2:05]

Dom’s Press-Pulse paper with Tom Seyfried from 2017: Press-pulse: a novel therapeutic strategy for the metabolic management of cancer

The press-pulse concept

  • It’s the idea of using ketone metabolic therapy (or therapeutic ketosis) and other modalities to compromise tumor growth and proliferation
  • This weakens the tumor making it more susceptible to be killed by other modalities

⇒ Example, the ketogenic diet combined with hyperbaric oxygen therapy (HBOT)

  • Being in a state of therapeutic ketosis…
    • Suppresses insulin signaling, which drives PI-3 kinase, lowers glucose availability to the tumor, 
    • It elevates ketone bodies which can not be readily utilized by most cancers as a source of fuel
    • Ketones also impair antioxidant pathways that the tumors use to defend itself (e.g., the pentose phosphate pathway generates more glutathione in cancer cells and that is being fed by glucose)
  • *In summary—if you reduce glucose availability and inhibit insulin, which suppresses glycolysis, you’re creating a scenario where if you give an oxidative challenge with hyperbaric oxygen therapy, you can potentially kill the cancer cells

The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer Poff et al., 2013

  • In 2013, Dr. Angela Poff studied the ketogenic diet with hyperbaric oxygen 
  • Hyperbaric oxygen was delivered at 2.5 atmospheres of oxygen, 90 minutes, 3 times per week
  • The ketogenic diet combined with the hyperbaric oxygen protocol proved to decrease tumor burden and extend the lifespan in VM-M3 mouse model (developed by Thomas Seyfried)

Tom Seyfriend’s paper: The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer

  • Supports the idea that a lower the glucose-ketone (ideally in the 1 to 2 range) slows tumor growth and proliferation and makes it more vulnerable to HBOT

Many different things that you can combine in press-pulse therapy

  • A weakened tumor from therapeutic ketosis may be more vulnerable to a number of other cancer specific metabolic drugs—

Dom’s 2017 review was more of a preclinical concept, but now there are a number of relevant papers coming out—

  • Valter Longo’s mouse study showed a remarkable effect using a nontoxic combination of a fasting-mimicking-diet (FMD) with IV vitamin C against KRAS mutated cancers
  • Another paper showed a decrease in tumor burden in a woman with metastatic thymoma treated with a ketogenic diet and fasting combined with prednisone and other immune based therapies

Figure 1. PET image showing decrease in tumor burden in a woman with metastatic thymoma treated with a ketogenic diet and fasting combined with prednisone and other immune based therapies. Image credit: Phillips et al., 2020

Potential role for vitamin C in cancer treatment [12:45]

Vitamin C as a PRO-oxidant?

  • Most people think of vitamin C as an antioxidant
  • But high concentrations of vitamin C can be a prooxidant–making it relevant in cancer treatment

{end of show notes preview}

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Dom D'Agostino, Ph.D.

Dom is an Associate Professor at the University of South Florida where he teaches at the Morsani College of Medicine and the Department of Molecular Pharmacology and Physiology. He focuses on neuropharmacology, medical biochemistry, physiology, neuroscience, neuropharmacology. Dom holds a PhD in neuroscience and Physiology. [See full bio at KetoNutrition.org]

Twitter: @DominicDAgosti2

Instagram: @dominic.dagostino.kt

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  1. Such great timing. My 28 year old daughter just started HBOT 4 months following end of chemo and radiation to pelvis for Ewings sarcoma. She also takes metformin and several other off label drugs plus supplements.

  2. Hi Peter/Bob,

    Thank you for such an informative podcast. I’ve been interested in the ketogenic diet ever since reading Peter’s blog posts about his cycling performance followed shortly by Dom D’Agostino’s early HBOT combined with keto research. I was wondering if any of you would know about the ketogenic diet for treatment of lymphoma?
    My grandad has Non-Hodgkins type lymphoma and is currently receiving mild treatment (started with radiotherapy and now drugs) at spaced intervals. He has already tried fasting in the treatment interims, which he noted increased his mental clarity and general feeling of wellbeing/health. However, it is hard to sustain for a long period of time so I was wondering if a keto diet has maybe been shown to help with this type of cancer. This would be in conjunction with his current treatment, so if there is any research/anecdotal reports you may know of where the keto diet helps with NHL it would be great to hear about.

  3. unfortunately, for me, I tried everything (e.g., a fasting mimicking diet (avg. ~1200 cal/day) w/ 8/16 time restricted feeding along with very low carbs, all for ~5 mo w/ lots of physical exercise) and I never could produce elevated ketones, and unless I ate simple carbs my glucose would daily go hypoglycemic (10 years and control well with natural/strategic means. So, I figure my very bad Type 2 diabetes must impair my ability to burn fat as a fuel, and has impaired my ability to convert stored glucagon into blood glucose, b/c after ~16hrs of fasting my glucose always steadily drops ever deeper into hypoglycemia until I cannot think/function, almost like how Type 1 diabetes people are. Can anyone explain what is maybe stopping Ketone production for me?

    What is working for me are zone 3+ workouts will release stored glucagon into blood glucose during otherwise hypoglycemia fasting. I confirmed this effect in recent research literature and some Attia podcasts mention it. I plan on trying this strategy to get to fasting for at least 1 day, and to maybe slowly help adapt/fix my diabetes messed up fat burning system over the long term.

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